Method for treating an allergic or inflammatory disease

ABSTRACT

This invention is to provide an agent for therapy and prevention of allergic diseases which has no adverse action, shows a high safety even by administration for a long period and is able to be utilized to food and/or beverage, cosmetics, etc. which are used daily. To be specific, it provides antiallergic agent and anti-inflammatory agent characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient; a method for the addition of an antiallergic agent for oral administration or an anti-inflammatory agent for oral administration which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient to food and/or beverage for prevention, suppression and mitigation of allergic symptoms or inflammatory symptoms.

This application is a Division of application Ser. No. 10/131,211 Filedon Apr. 25, 2002, now U.S. Pat. No. 6,638,524 which was a Continuationof application Ser. No. 09/778,820, filed on Feb. 8, 2001, (Now U.S.Pat. No. 6,491,943).

FIELD OF THE INVENTION

The present invention relates to a pharmaceutical agent as well as foodand/or beverage and cosmetics containing at least one polyphenolcompound selected from strictinin and methylated derivatives thereof asan effective ingredient and, more particularly, it relates to a foodhaving an action of suppressing the immediate-type and delayed-typeallergy, to a pharmaceutical agent with an object of improving theallergy and to a cosmetic agent containing the same.

BACKGROUND OF THE INVENTION

In recent years, an increase in allergic diseases has been noted and itis reported that, in about one-third of the newborn babies, onset ofatopic dermatitis or asthma is observed. A drastic increase in onset ofpollinosis has been becoming a big social problem as well.

It has been believed that changes of environment surrounding us such aswesternization of meals, air pollution, food additives and excessivestress are the causes of an increase in such allergic symptoms.

In view of the immunological competent cell and immunoglobulin which areparticipated therein, allergic reaction is classified into from type Ito type IV. Diseases represented by allergic rhinitis and bronchialasthma belong to the allergic reaction of type I where IgE antibody isproduced in large quantities when exposed to allergen and chemicalmediators such as histamine, leukotrienes and prostaglandin are producedand released from mast cells and basophils via the said IgE antibodywhereby dilation of blood vessel, promotion of blood vesselpermeability, shrinking of bronchial smooth muscles, stimulation ofnerve terminals, etc. are induced. Therefore, for the therapy ofallergic diseases of type I, antihistaminic agents and antiallergicagents having an action of suppressing the liberation of chemicalmediators from mast cells have been used.

However, antihistaminic agents and basic antiallergic agents haveadverse actions such as drowsiness, thirst, gastrointestinal troubles,etc. and their continuous administration for a long period causes aproblem.

Allergic reaction of type IV is a reaction of a delayed type in which Tcells are participated where T cells receiving an antigen informationvia antigen-presenting cells such as Langerhans cells and macrophageproduce and release various cytokines whereby an inflammation reactionof a delayed type takes place due to accumulation of eosinophils andmacrophages.

Allergic contact dermatitis is a typical disease which occurs due to anallergic reaction of type IV. Steroid agents are used for the therapy ofallergic diseases of type IV and such steroid agents suppress theproduction of cytokine in T cells and show a dramatic effect for thetherapy of eczema. On the other hand however, there is a possibilitythat they cause severe adverse actions such as a decrease inadrenocortical function, flushing of the skin, atrophy and dilation ofcapillaries by their administration for a long period.

In the meanwhile, tea is a typical luxurious beverage and has been drunkby many people during more than 2000 years. It has been also known thattea has various physiological functions and, for example, itsantioxidative action, antitumor action, suppressive action tocarcinogenesis, antibacterial action, antiviral action and anticariousaction have been reported.

With regard to an allergic action, there have been exemplified thetherapeutic agent to the allergic reaction of type I as an antiallergicagent mainly comprising an extract from oolong tea using an action ofsuppressing the histamine liberation from mast cells as an indicator inJapanese Patent Laid-Open No. 258726/1991; the effective cases ofnatural caffeine for the promoting reaction of blood vessel permeabilityin allergic symptom of type I in Japanese Patent Laid-Open No.17865/1995; and therapeutic agents such as antiallergic agent,anti-inflammatory agent, anti-atopic dermatitis agent and anti-psoriasiswhere an extract of oolong tea is an effective ingredient in JapanesePatent Laid-Open Nos. 77231/1998 and 175874/1998.

It has been further reported that green tea catechins such asepigallocatechin gallate and epicatechin gallate suppress the liberationof histamine from mast cells in abdominal cavity of rat (Journal ofJapanese Society for Food Science and Technology, Vol.42, No. 11, p.952-958, 1955; and Allergy, Vol. 52, No. 1, pp. 58-64, 1997). However,there has been no report that polyphenols such as strictinin suppressthe production of IgE by B cells which is an origin of allergicreaction.

Pharmaceutical agents for allergic diseases have been developed and usedfor the therapy already but, since they have adverse actions, there hasbeen a strong demand for antiallergic agents derived from naturalproducts where a long-term administration is possible, safety is highand no adverse reaction takes place.

Thus, an object of the invention is to provide a therapeutic andpreventive agent for allergic diseases which has no adverse action,shows a high safety even by a long-term administration and is able to beutilized for food and/or beverage and cosmetic agent which are useddaily.

In order to solve the above-mentioned problems, the present inventorshave carried out a screening of substances having antiallergic actionusing a suppressive action for the production of IgE as an indicationand have found that polyphenols such as strictinin exhibits such aneffect and, based upon such a finding, the invention has been achieved.

SUMMARY OF THE INVENTION

The invention mentioned in claim 1 is an antiallergic agent which ischaracterized in containing, as an effective ingredient, at least onepolyphenol selected from strictinin and methylated derivatives thereof.

The invention mentioned in claim 2 is an anti-inflammatory agent whichis characterized in containing, as an effective ingredient, at least onepolyphenol selected from strictinin and methylated derivatives thereof.

The invention mentioned in claim 3 is the antiallergic agent accordingto claim 1 wherein the antiallergic agent is that for oraladministration.

The invention mentioned in claim 4 is the anti-inflammatory agentaccording to claim 2 wherein the anti-inflammatory agent is that fororal administration.

The invention mentioned in claim 5 is food and/or beverage containing anantiallergic agent for oral administration or an anti-inflammatory agentfor oral administration which is characterized in containing, as aneffective ingredient, at least one polyphenol selected from strictininand methylated derivatives thereof.

The invention mentioned in claim 6 is a method for the addition of anantiallergic agent for oral administration or an anti-inflammatory agentfor oral administration which is characterized in containing, as aneffective ingredient, at least one polyphenol selected from strictininand methylated derivatives thereof to food and/or beverage forprevention, suppression and mitigation of allergic symptoms orinflammatory symptoms.

The invention mentioned in claim 7 is a cosmetic agent containing anantiallergic agent for external use or an anti-inflammatory agent forexternal use which is characterized in containing, as an effectiveingredient, at least one polyphenol selected from strictinin andmethylated derivatives thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow chart showing an example of a method for thepurification of strictinin;

FIG. 2 shows an influence of each of the fractionated fractions on aCεGT-inducible expression by IL-4;

FIG. 3 shows an influence of strictinin on a CεGT-inducible expressionby IL-4 in human B cell line DND 39; and

FIG. 4 shows an influence of strictinin on a CεGT-inducible expressionby IL-4 in human peripheral blood lymphocytes.

DETAILED DESCRIPTION OF THE INVENTION

Strictinin according to the invention is a compound represented by thefollowing structural formula and, in addition to the said compound, apolyphenol which is a methylated derivative or a mixture thereof may beused in the present invention as well. Examples of the polyphenol arethose where galloyl group, digalloyl group, trigalloyl group,hexahydroxyphenoyl group, 3-O-methylgalloyl group or 4-O-methylgalloylgroup is introduced into at least one of the hydroxyl groups at C1 to C4and C6 of glucose.

Tea (Camellia sinensis) has been drunk from ancient time and has beenalways taken for a long period and it has been noted that tea has no badaffection to human body but is a beverage with a very high safety.Accordingly, the tea leaf extract mainly comprising a polyphenolcompound such as strictinin used in the invention can be accepted asbeing taken without anxiety.

The polyphenols such as strictinin used in the invention can beseparated and collected from a polyphenol fraction obtained by anextraction of dried tea leaves such as “yabukita” tea leaves with anaqueous solvent. When the extract is utilized in and taken as foodand/or beverage, cosmetics, etc. in its final stage, it is preferredfrom the standpoint of safety that water, ethanol or a mixture thereofis used as a solvent.

Although there is no particular limitation for the ratio (by weight) ofthe tea leaves to the solvent, the ratio from 5 to 100 parts of thesolvent to 1 part of tea leaves is preferred. With regard to thetemperature for the extraction, there is no particular limitation aswell and, usually, the range of from the room temperature to the boilingpoint of the solvent under an atmospheric pressure is preferred in viewof the operation. Time for the extraction is preferably with in a rangeof from 10 minutes to 6 hours.

The tea leaf extract mainly comprising polyphenols such as strictininused in the invention may be administered per se either as it is orafter appropriately diluting with water or the like. It is also possiblethat it is made into a pharmaceutical preparation together with acommonly used pharmaceutical carrier. For example, the above-mentionedextract or the like can be made into a liquid preparation for oral usesuch as a syrup or made into a solid preparation for oral use such astablets, capsules, granules or diluted powder after processing intoextract, powder, etc. followed by compounding with a pharmaceuticallyacceptable carrier. With regard to the pharmaceutically acceptablecarrier, various organic or inorganic carrier substances which have beencommonly used as the materials for pharmaceutical preparations may beused and they are compounded as vehicles, lubricant, binder,disintegrator, etc. in a solid preparation or as solvent, excipient,suspender, binder, etc. in a liquid preparation. If necessary, additivesfor pharmaceutical preparations such as antiseptic, antioxidant,coloring agent, sweetener, etc. may be used as well.

Suitable examples of the vehicles or excipient are lactose, white sugar(sucrose), D-mannitol, starch, crystalline cellulose and light anhydroussilicic acid. Suitable examples of the lubricant are magnesium stearate,calcium stearate, talc and colloidal silica. Suitable examples of thebinder are binding cellulose, white sugar, D-mannitol, dextrin,hydroxypropyl cellulose, hydroxypropyl methyl cellulose andpolyvinylpyrrolidone.

Suitable examples of the disintegrator are polyethylene glycol,propylene glycol, D-mannitol, benzylbenzoate, ethanol, trisaminomethane,cholesterol, triethanolamine, sodium carbonate and sodium citrate.Suitable examples of the solvent are purified water, ethyl alcohol andpropylene glycol. Suitable examples of the suspending agent aresurface-active agent such as ethanolamine stearate, sodiumlaurylsulfate, laurylaminopropionic acid, lecithin, benzalkoniumchloride, benzethonium chloride and glycerol monostearate andhydrophilic high-molecular compounds such as polyvinyl alcohol,polyvinylpyrrolidone, carboxymethyl cellulose, methyl cellulose,hydroxymethyl cellulose, hydroxyethyl cellulose and hydroxypropylcellulose.

Suitable examples of the antiseptic are p-hydroxybenzoates,chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid andsorbic acid. Suitable examples of the antioxidant are sulfites andascorbic acid.

The tea leaf extract mainly comprising polyphenols such as strictininused in the present invention may be administered either as it is or theextract is made into dry extract or powder to make in a form of foodand/or beverage. It is compounded with a commonly used material for foodand/or beverage and a carrier or the like which is acceptable for themanufacture of food and/or beverage and examples of the beverage aremixed tea drink, carbonate beverage, fruit beverage, lactic acidbacteria beverage, sport beverage and soybean milk. Examples ofconfectionery are biscuit, chocolate, candy, chewing gum, snack cake,fried cake, western unbaked cake, Japanese cake, ice cream and jellycake. Examples of food are bread, noodle; processed soy bean productssuch as soybean curd; milk products such as yogurt and butter; meatproducts such as ham and sausage; omelet; fish meat paste products suchas kamaboko; condiments such as sauce, dressing, mayonnaise and fishflour; and meals such as curry, stew, hamburger and soup. They can beprepared by conventional methods.

Examples of the carrier which is acceptable in the manufacture of foodand/or beverage are sweeteners such as sugar, glucose, fructose,isomerized liquid sugar, fructooligosaccharide, aspartame, sorbitol andstevia; coloring agents such as red cabbage dye, grape rind dye,elderberry dye, caramel, gardenia dye, corn dye, saffron dye andcarotene; preservatives such as decomposed pectin, benzoic acid, sorbicacid, p-hydroxybenzoates and potassium sorbate; pastes such as sodiumalginate, propylene glycol alginate, calcium cellulose glycolate andsodium cellulose glycolate; antioxidants such as L-ascorbic acid,tocopherol, erythorbic acid and rutin; coloring former such as ferroussulfate, sodium nitrite and potassium nitrite; bleaching agents such assodium hydrogen sulfite and potassium metabisulfite; quality maintainingagents such as propylene glycol; quality improving agents such asL-cysteine hydrochloride and calcium stearyllactate; inflating agentssuch as ammonium chloride, potassium hydrogen d-tartrate, ammoniumcarbonate, potassium carbonate, sodium hydrogen carbonate and alum;emulsifiers such as lecithin, sphingolipid, vegetable sterol, soybeansaponin, sodium alginate, propylene glycol alginate, sodium caseinate,glycerol fatty acid ester, sucrose fatty acid ester and sorbitan fattyacid ester; emulsion stabilizers such as sodium chondroitin sulfate;flavoring agents such as lemon oil, eucalyptus oil, peppermint oil,vanilla extract, orange oil, garlic oil, ethyl acetoacetate,anisaldehyde, ethylvanillin, cinnamic acid, citronellyl acetate, citral,vanillin, butyl butyrate and esters; enrichers such as L-ascorbic acid,L-asparagine, L-alanine, inositol, L-glutamine, carotene, tocopherol,vitamin A, folic acid, iron citrate, heme iron and non-calcined calcium;improving agents for wheat flour such as benzoyl peroxide, ammoniumpersulfate and chlorine dioxide; bactericides such as bleaching powder,hydrogen peroxide and hypochlorous acid; base materials for chewing gumsuch as methyl acetylricinolate, ester gum, vinyl acetate resin,polyisobutylene and polybutene; adherence preventers such as D-mannitol;binders such as sodium acidic pyrophosphate, potassium pyrophosphate andsodium pyrophosphate; acidic taste agents such as adipic acid, citricacid, gluconic acid, succinic acid, D-tartaric acid, lactic acid andDL-malic acid; seasonings such as fish/shellfish extract, yeast extract,sea tangle extract, soybean sauce, tomato puree, meat extract, mirin(Japanese sweet rice wine), fruit puree, dried bonito, sodiumL-aspartate, DL-alanine, L-arginine, L-glutamate, disodium 5′-inosinate,trisodium citrate, L-glutamic acid, sodium L-glutamate, succinic acid,L-tartaric acid and sodium lactate.

The tea leaf extract mainly comprising polyphenols such as strictininaccording to the invention is diluted with water or the like,concentrated or made into powder or granules followed by making intopharmaceutical preparation together with known pharmaceutical carriersto give the dosage forms such as aerosol, liquid, extract, suspension,emulsion, ointment, poultice, liniment or lotion. Or, if necessary,aqueous component, surface-active agent, oily component, solubilizer,moisturizer, powder component, alcohol, pH adjusting agent, antiseptic,antioxidant, thickener, dye, pigment, perfume, etc. which are known tobe used for cosmetics, semi-pharmaceuticals and pharmaceuticals areappropriately selected whereupon a desired form is prepared.

As an externally applied agent for the skin, it is possible to make intothe form of, for example, lotion, gel, emulsion, ointment, etc. wherebyit is possible to provide as a cosmetic agent in various forms includingcosmetic lotions such as softening cosmetic agent and astringentcosmetic lotion; creams such as emollient cream, moisture cream andmassage cream; milky lotions such as emollient milky lotion, nourishingmilky lotion and cleansing milky lotion; make-up cosmetics such asface-washing agent, skin cleanser, foundation, eye color, cheek colorand lipstick; hair cosmetics such as shampoo, rinse, hair treatment,hair cream, hair dressing, hair tonic, pilatory and hair growing agent;bathing agents such as bath oil, bath salt and foam bath; etc.

In the present invention, polyphenols such as strictinin may be used inan appropriate amount taking the object for use, etc. into considerationand, for example, in the case of antiallergic agent or anti-inflammatoryagent, the amount of 5-100 mg/kg or, preferably, 10-50 mg/kg per day isappropriate.

When used in food and/or beverage, polyphenols such as strictinin whichare effective ingredients are used within a range of 5-100 mg/kg or,preferably, 10-50 mg/kg per day. Similarly, in the case of cosmetics,polyphenols such as strictinin which are effective ingredients are usedwithin a range of 5-100 mg/kg or, preferably, 10-50 mg/kg per day.

Incidentally, in any of the above cases, the amount may be used oncedaily or by dividing into several times a day.

Antiallergic agent and anti-inflammatory agent of the present inventionand cosmetics containing the same are effective for prevention,suppression or mitigation of inflammation and the symptoms caused byallergic reaction. In addition, since such pharmaceutical agents containpolyphenol compounds such as strictinin contained in tea as effectiveingredients, safety is high and no toxic adverse action is noted tohuman body even by administration for a long period whereby they can bedaily taken. Further, when food and/or beverage containing a tea extractmainly comprising polyphenol compounds such as strictinin is dailytaken, it is useful for prevention and mitigation of the symptoms byallergic reaction.

EXAMPLES

In order to illustrate the invention in detail, representative Examplesand Experimental Examples will be given as hereunder although theinvention is not limited thereto.

Experimental Example 1 Extraction of Polyphenol Fraction from VariousTea Leaves (Tea Leaf Extract)

Tea leaves (100 g) dried with microwave were extracted with 50% methanoland the extracted fraction was extracted with 30% chloroform. Itsaqueous phase was further extracted with ethyl acetate and the ethylacetate layer after the extraction was fractionated using an ODS column.An example of the method for the purification of strictinin is shown inFIG. 1. The fractionated fractions were named Fr. 1 to 5, respectively.All of Fr. 1 to 5 were once freeze-dried and then Fr. 1 to 2, Fr. 3 to 4and Fr. 5 were dissolved in water, 0.2% DMSO and 0.1% DMSO, respectivelyso that each fraction was made 1 mg/mL.

Experimental Example 2 Identification of Active Fractions

Each of Fr. 1 to 5 in Experimental Example 1 was evaluated for itsantiallergic action in vitro by a method for the expression of atranscript of an IgE heavy chain germline transcript which was toinvestigate the suppression of IgE production in human B cells (IgEclass switch suppression). This is a method utilizing the fact that,when human B cells are stimulated by IL-4 to induce the production ofIgE, a transcription is started from the upstream intron correspondingto an ε region (Cε) in the constant domain gene of the Ig gene whereupona transcript (CεGT: germline transcript) is expressed and, after that, aclass switch of IgE is resulted by a DNA recombination. CεGT is an RNAwhich is always expressed before the IgE production is induced and theexpressed amount of CεGT is proportional to the class switch amount ofthe IgE gene. Therefore, when the degree of expressed amount of CεGT isdetected, it is possible to estimate the IgE class switch amount.

A method for the expression of an IgE heavy chain germline transcriptwas carried out according to the following procedures.

Human B cell line DND 39 (available from Hayashibara BiochemicalLaboratory) was prepared into 1×10⁵ cells/mL and stimulated by addingIL-4 thereto to make the final concentration 25U/mL. At that time, eachof Fr. 1 to 5 prepared in Experimental Example 1 in a concentration of10 μg/mL was added together with IL-4.

In the meanwhile, IL-4 (final concentration: 25 U/mL) and 2 ng/mL of atransforming growth factor β (TGF-beta; manufactured by Peprotech) wereadded to the above human cell line and the mixture was used as apositive control for suppressing the expression of CεGT.

They were incubated for 48 hours and centrifuged (300 ×g, 37° C.) tocollect the cells and the total RNA was extracted with 1 mL of a reagentfor collection and extraction of RNA (trade name: Trizol; manufacturedby Gibco BRL).

Then, a cDNA library was prepared according to the following procedure.First, concentration of the extracted total RNA was measured by anabsorptiometer, a portion of 10 μg was taken in a 0.6 mL tube and waterwas added thereto to make 11.8 μL. To this were added each 1.0 L of a0.5 μg/μL oligo dT primer and a 20 μM CεGT antisense primer. The tubewas incubated at 70° C. for 10 minutes and quickly cooled in ice for 10minutes and annealed to anneal mRNA, oligo dT primer and CεGT antisenseprimer. This was mixed with 2.0 μL of an RNase-free 10 mM dNTP(manufactured by Amersham), 4.0 μL of 5×buffer attached to anMMLV-reverse transcriptase (manufactured by Amersham), 0.1 μL of anRNase inhibitor (manufactured by Takara Shuzo) and 0.1 μL (finalconcentration: 20-200 units/tube) of an MMLV-reverse transcriptase. Themixture was incubated at 37° C. for 1 hour to synthesize cDNA. Thesynthesized cDNA was amplified by a PCR. Sense and antisense primerswere prepared based upon a base sequence of human GAPDH and CεGTregistered at the Gene Bank. The structures are shown in the SequenceListing. Thus, a CεGT sense primer, a CεGT antisense primer, a humanGAPDH sense primer and a human GAPDH antisense primer are shown in SEQID NO:1, NO:2, NO:3 and NO:4, respectively.

CεGT-DNA was amplified using the said primer by a polymerase chainreaction (PCR) method. As a template for the PCR, 1 μL of an originalsolution of cDNA was used and, for the detection of CεGT, 0.8 μL of 10mM dNTP, 0.5 μL of sense primer, 0.5 μL of antisense primer, 0.1 μL ofAmpliTaq Gold (manufactured by Perkin Elmer) and 1 μL of 10×bufferattached to the AmpliTaq Gold were mixed and distilled water was addedthereto to make the total volume 10 μL.

For the detection of GAPDH, 0.8 μL of 10 mM dNTP, 1 μL of MgCl₂, 0.5 μLof sense primer, 0.5 μL of antisense primer, 0.1 μL of Taq polymerase(manufactured by Fermentas) and 1 μL of 10×Taq buffer attached to theTaq polymerase were mixed and distilled water was added thereto to makethe total volume 10 μL.

A PCR was carried out using a GeneAmp PCR System 2400 (manufactured byPerkin Elmer) and the condition therefor was as follows. Thus, for thedetection of CεGT, a cycle of 95° C. for 30 seconds, 60° C. for 30seconds and 72° C. for 30 seconds was conducted for 15 cycles and,finally, a reaction was carried out at 72° C. for 7 minutes. For thedetection of GAPDH, a cycle of 95° C. for 30 seconds, 60° C. for 30seconds and 72° C. for 30 seconds was conducted for 10 cycles and,finally, a reaction was carried out at 72° C. for 7 minutes. After that,the resulting PCR product was subjected to an electrophoresis using anagarose gel for separation (concentration: 1%; manufactured by SawadiTechnology). After completion of the electrophoresis, it was transcribedto a plus-charged Nylon membrane (manufactured by Amersham) (a southerntransfer).

After that, a hybridization was carried out on the Nylon membrane towhich the migrated pattern was transcribed using an oligo DNAfluorolabeled with CεGT-DNA which was amplified for 15 times in theabove-mentioned PCR [which was prepared in such a manner that anoligonucleotide (SEQ ID NO:5 of the Sequence Listing) was picked outfrom a region pinched by the above-mentioned sense and antisense primersused for the PCR based on a base sequence of human CεGT and then theoligonucleotide is applied to an oligo labeling kit (manufactured byAmersham)] as a probe. After the hybridization, a reaction with CDP-Star(Amersham) which was a fluorescence detecting agent was carried out andthe expressed amount of CεGT was measured from the resultingfluorescence intensity. FIG. 2 shows an influence of each fraction onCεGT inducible expression by IL-4 in the human B cell line DND 39. Inthe drawing, GAPDH means glyceraldehyde-3-phosphodehydrogenase and □shows a control.

As will be apparent from FIG. 2, the expressed amount of CεGT wassuppressed in the fraction of Fr. 3 as compared with other fractions.From that fact, it was found that an active component was available inthe fraction of Fr. 3 and, after that, the fraction was finelyfractionated using an ODS column whereupon one of the fractions wasfound to be a fraction containing strictinin only.

Experimental Example 3 Measurement of Antiallergic Activity in Human BCell Line

Strictinin which was identified as an active component in ExperimentalExample 2 was used for measuring the antiallergic activity in human Bcell line according to the same way as in the method for the expressionof an IgE heavy chain germline transcript mentioned in ExperimentalExample 2. Incidentally, strictinin was added at the same time withIL-4. The adding concentrations of strictinin were 1, 10 and 25 μM. FIG.3 shows an influence of strictinin on the CεGT inducible expression byIL-4 in the human cell line DND 39. In the drawing, GAPDH showsglyceraldehyde-3-phosphodehydrogenase and □ shows a control.

As shown in FIG. 3, it was apparent that, in the human B cell line,strictinin strongly suppressed the IgE class switch by addition of IL-4.Since IgE is an immunoglobulin deeply participating in the allergicreaction, the fact that IgE class switch is suppressed means thatantiallergic activity is available.

Experimental Example 4 Measurement of Antiallergic Activity in HumanPeripheral Blood Lymphocytes

Human peripheral blood normal cells (monocytes; separated from the bloodwhich was collected from a healthy human volunteer) was used instead ofthe human B cell line DND 39 of Experimental Example 3 and anantiallergic activity was measured by the same way as in the method forthe expression of an IgE heavy chain germline transcript mentioned inExperimental Example 2. Like in Experimental Example 2, strictinin wasadded at the same time with IL-4. Incidentally, the adding concentrationof strictinin was made 25 μM. FIG. 4 shows an influence of strictinin onthe CεGT inducible expression by IL-4 in the human peripheral bloodlymphocytes. In the drawing, GAPDH showsglyceraldehyde-3-phosphodehydrogenase and □ shows a control.

As shown in FIG. 4, strictinin strongly suppressed the IgE class switchby addition of IL-4 in the human peripheral blood lymphocytes and wasnoted to have an antiallergic activity.

Example 1 Manufacture of Candy

Candy was manufactured by a conventional method using the followingmaterials. As to a polyphenol fraction containing strictinin, etc., Fr.3 in Experimental Example 1 was used (the same one was used in all thefollowing Examples as well).

Powdery sorbitol 97.7 g Perfume  0.2 g Sorbitol seed 0.05 g Polyphenolfraction containing strictinin, etc. 0.05 g Total  100 g

Example 2 Manufacture of Chewing Gum

Chewing gum was manufactured by a conventional method using thefollowing materials.

Gum base   20 g Calcium carbonate    2 g Stevioside  0.1 g Polyphenolfraction containing strictinin, etc.  0.05 g Lactose 76.85 g Perfume   1 g Total   100 g

Example 3 Manufacture of Bathing Agent

A bathing agent containing a tea leaf extract mainly comprisingstrictinin was manufactured by a conventional method using the followingmaterials.

Dry sodium sulfate  53 g Sodium hydrogen carbonate  40 g Light calciumcarbonate  1 g Silicic acid anhydride  1 g Polyphenol fractioncontaining strictinin  5 g Perfume a little Pigment a little Total 100 g

1. A method for treating an allergic or inflammatory disease comprisingadministering to a subject in need thereof an amount of purifiedstrictinin or a methylated derivative thereof effective to treat saidallergic or inflammatory disease.
 2. The method of claim 1 comprisingtreating a subject having an allergic disease.
 3. The method of claim 1comprising treating a subject having an inflammatory disease.
 4. Themethod of claim 1 that comprises administering purified strictinin. 5.The method of claim 1 that comprises administering an purifiedmethylated derivative of strictinin.
 6. The method of claim 1, whereinsaid purified strictinin or methylated derivative of strictinin isextracted from tea.
 7. The method of claim 1 that comprisesadministering a dosage of strictinin or a methylated derivative thereofranging from 5 to 100 mg/kg.
 8. The method of claim 1 that comprisesadministering a dosage of strictinin or a methylated derivative thereofranging from 10 to 50 mg/kg.
 9. The method of claim 1, wherein saidstrictinin or methylated derivative of strictinin is administeredorally.
 10. The method of claim 1, wherein said strictinin or methylatedderivative of strictinin is administered externally.
 11. The method ofclaim 1 comprising administering a food comprising strictinin or amethylated derivative of strictinin.
 12. The method of claim 1comprising administering a beverage comprising strictinin or amethylated derivative of strictinin.
 13. A method for purifyingstrictinin or a methylated derivative thereof from tea comprising: (a)extracting tea leaves with an aqueous methanol or ethanol solution, (b)extracting the aqueous methanol or ethanol solution obtained in (a) withan aqueous chloroform solution, (c) extracting the aqueous phase from(b) with ethyl acetate, (d) fractionating the ethyl acetate layer from(c) on an ODS column and (e) recovering one or more fractions containingpurified strictinin or a methylated derivative thereof.
 14. A purifiedstrictinin obtained by the method of claim
 13. 15. A purified methylatedderivative of strictinin obtained by the method of claim 13.